ANNALS O F CLINICAL AND LABORATORY SCIENCE, Vol. 29, No. 4Copyright © 1999, Institute for Clinical Science, Inc.

Pleomorphic Large Cell Sarcoma o f the Spleen with Riiabdomyosarcomatous Differentiation*

JERRY Z. GONG, M .D .,1 JAMES D. SULLIVAN, M .D .,2

SAUL TEICH BERG , Ph.D .,1 and STEVEN I. HAJDU, M .D .1

Division of Surgical Pathology and Cytopathology, Department o f Pathology,1

and the Department of Surgery,2 North Shore University Hospital,

Manhasset, New York 11030

ABSTRACT

An unusual case is reported of pleomorphic large cell sarcoma of the spleen with rhabdomyosarcomatous differentiation in a 34-year old male. According to our knowledge, such a neoplasm has never been reported in the literature.

Introduction

The spleen is an organ o f mesenchymal derivation in which sarcomas may be found. However, primary sarcoma of the spleen is rare. Neoplasms of the spleen with vasoforma­tive elements, fibroblasts, and adipose cells have been reported in the literature.1 Primary sarcom a with skeletal m uscle d ifferen tia­tion, according to our knowledge, has never been reported.

C ase Report

A 34-year old white male presented with persistent cough, fever, and night sweat. Clini­cal evaluation with consideration of recent travel to Malaysia included peripheral blood

* Address correspondence and reprint requests to: Steven I. Hajdu, M.D., North Shore University Hospital, Manhasset, New York 11030, U.S.A.

Key words: pleomorphic large cell sarcoma, pleomor­phic rhabdomyosarcoma, spleen

Abbreviations: RMS, rhabdomyosarcoma

smear and bone marrow biopsy studies that showed no abnormality. CT scan of the abdo­men revealed massive splenomegaly [figure 1] and small intraheptic nodules. Lymphade- nopathy limited to the splenic hilium was also noted. Clinical and radiologic impressions were malignant lymphoma. On abdominal and retroperitoneal exploration, after the diagnosis of pleomorphic malignant tumor, favor sar­coma was rendered on intraoperative frozen section, splenectomy, distal pancreatectomy, retroperitoneal lymphadenectomy, and biopsy of the liver were performed. The patient had an uneventful postoperative course and was discharged one week after surgery, pending readmission for further treatment.

The spleen was massively enlarged, weigh­ing 3200 grams. The capsule of the spleen was intact bu t there were m ultiple subcapsular tum or nodules. The splenic vessels were pat­ent bu t they were compressed by enlarged hilar lymph nodes. The cut surface showed a large mass, measuring 20 x 16 x 10 cm., almost completely replacing the spleen. The

3030091-7370/99/0700-0303 $00.00 © Institute for Clinical Science, Inc.

304 G O N G , SULLIVAN, T E IC H B E R G , & HAJDU

F igure 1. CT scan shows a mass occupying the entire spleen.

tum or appeared pink to white, fleshy, with large areas of necrosis and multiple foci of hemorrhage [figure 2],

Microscopically, there was no distinct growth pattern. The tum or was composed of haphaz­ardly arranged pleomorphic cells with num er­ous elongated spindle cells and polygonal tumor giant cells. The tumor cells showed dis­

tinct cell borders. The cytoplasm was acido­philic and occasionally showed striations in elongated and giant cells but the majority of cells showed ground glass, rhabdoid appear­ance without distant features of muscle differ­entiation. The nuclei were enlarged and con­tained prom inent nucleoli. Atypical mitotic figures w ere frequent. T here w ere many

F igure 2. Gross appearance of the tumor. The enlarged spleen contains a mass measuring 20 x 16 x 10 cm. The tumor is characterized by solid nodules with areas of necrosis and hemorrhage.

LARGE C E L L SARCOMA O F T H E SPL EEN 305

binucleated and m ultinucleated round and pleomorphic neoplastic cells. Areas with apop- tosis and necrosis were many. Tum or cells w ere closely packed and the in tercellular matrix was sparse [figures 3,4].

Typical cytologic features of high grade p leom orphic sarcom a w ere evident. The tum or infiltrated the splenic capsule with microscopic extension into soft tissues and lymph nodes in the liilum of the spleen. Tumor emboli were found in the splenic vein. Small nodules excised from the omentum and the liver contained neoplastic cells similar to those in the spleen.

Immunohistochemical stains showed strong positive reaction for vimentin and focal posi­tive reaction for myoglobin. Smooth muscle actin, S-100 p ro tein and neuroendocrine, endothelial, hem atopoetic, epithelial, and germ cell markers were all negative.

U ltrastructurally , the cytoplasm o f the tum or cells contained fairly elaborate rough endoplasmic reticulum, Golgi apparatus, focal basal lamina as well as occasional elongated bundles of thin filaments. Within the elon­gated filament clusters a dark band, resem­bling the Z band of striated muscle, was evi­dent at focal sites [figure 5].

Cytogenetic study of neoplastic cells after routine plating showed a karyotype of 50-58, XY, with add (2 )(p ll), del(3), t(l;3)(p22;pl3), +4, +4, +5, +add(5)(pl5), +7, - 8, -13 , 2x del(15)(ql5q26), -Y, +X, random loss, +marker.

The patient was readmitted ten days after discharge because of progressive shortness of breath with acute worsening. Chest x-ray and CT scan showed massive left pleural effusion and two nodules, each measuring less than one centimeter, in the right upper lobe and the right middle lobe of the lung. Abdominal and retroperitoneal radiologic examinations showed no new findings. Chemotherapy with intrave­nous adriamycin was started for three days but discontinued because of progressive worsening of the clinical course due to respiratory insuf­ficiency, acidosis, and hyperkalem ia. The patient expired two weeks after admission.

D iscussion

Some of the soft tissue sarcomas are highly undifferenitated without clearly defined ori­gin. Many of these tumors remain as com­pletely primitive, undifferentiated sarcomas but others may undergo differentiation and develop into specific types of soft tissue sarco­

FlGURE 3. The tumor is composed of sheets of polygonal cells with scanty intercellular matrix. No distinct growth pattern is observed. (Haematoxylin-eosin, xlOO).

306 G O N G , SULLIVAN, T E IC H B E R G , & HAJDU

FIG U R E 4. Giant polygonal and strap cells are common features. (Haematoxylin-eosin, x400).

mas. The proportion of recognizable and spe­cific neoplastic elem ents can be variable and problematic. It is well known that cyto­plasmic cross-striation is a rare feature in both, pleomorphic RMS as well as in embryonal RMS. Gaffney et al2 failed to find cross- striation in 11 cases of pleom orphic rhab­domyosarcoma even though they showed posi­tive stains for myoglobin and desmin. Our case is comprised mostly of undifferentiated sarcomatous cells with approximately 5% of the cells showing rhabdomyosarcomatous fea­

tures. These cells stained positive for myoglo­bin and showed ultrastructural evidence of cytoplasmic myofilaments Hence, we feel that it is proper to define the neoplasm as pleomor­phic large cell sarcoma with rhabdomyosarco­matous differentiation.

M alignant soft tissue neoplasm s of the spleen are rare. Angiosarcoma is considered the most frequent primary sarcoma followed by malignant fibrous histiocytoma and liposar- coma.1'3 Inflammatory processes in the spleen which mimic soft tissue tumors have also been

FIG U R E 5. Electron micrograph of a neoplastic cell with an elongated bundle of relatively parallel thin filaments. Note the alignment of the filaments to form a Z band-like dense structure perpendicular to the filaments (arrow). Other suggestive bands are also present (x63,000).

LARGE C E L L SARCOM A O F T H E S PL EEN 307

reported.4 Hajdu3 studied 121 cases of pleo­morphic RMS and found that the most fre­quent locations were thigh (37%), shoulder (11%), arm (9%), leg (9%), and chest wall (7%). Primary pleomorphic RMS in spleen was no t found. H e also studied m etasta­tic p leom orphic RMS in autopsied cases. Among 25 cases with metastasis, there were only two cases with metastasis to the spleen. In both cases, the métastasés were microscopic foci.3 Overall, metastasis o f soft tissue sarco­mas to the spleen was far less frequent than metastasis to other major organs. In only 13 of 151 autopsied cases were métastasés to the spleen identified.3

The present case showed typical features of primary malignant soft tissue neoplasm. His­tologically, the tum or was composed of a large solid mass with frequent necrosis and hemor­rhage. Clinically, the tum or was characterized by a rapidly expanding mass with documented liver and pulm onary métastasés. R epeated whole body com puted tomography scan and ultrasonography studies failed to reveal pri­mary site other than the spleen. These find­ings, together with pathologic observations, strongly suggest that the spleen is the most likely primary site of the tumor.

Although the etiology o f primary splenic sar­comas is uncertain, it is believed that malig­nant fibrous histiocytoma, angiosarcoma, and liposarcoma develop from primitive mesoder­mal elem ents.1 Splenic sarcoma with rhabdo- myosarcomatous differentiation as well as classic pleom orphic RMS have never been reported in the literature, hence their etiology has never b een stud ied . R habdom yosar- comatous differentiation of uterine5 and soft tissu e6,7,8 neoplasm s has b een rep o rted . Reports of RMS in organs devoid of skeletal m uscle suggest g row th and d if fe re n tia ­tion from primitive undifferentiated mesen­chymal tissue.9,10,11

In our case, in tracellular striations and primitive myofilaments were only observed in a few cells. Despite positive vimentin reaction in almost every cell, few cells showed positive reaction for myoglobin. These findings suggest that this tum or represents early stage arrest of

growth in the spectrum of progressive devel­opm ent from undifferentiated sarcoma, which lacks specific intracellular organelles, to differ­entiated pleom orphic RMS which contains cytoplasmic myoglobin and myofilaments.

A distinct pattern of t(2;13) translocation has been repo rted in alveolar and em bryonal RMS.12 Although our case showed multiple cytogenetic abnormalities, it lacked this trans­location. However, another common finding in embryonal RMS with rearrangement of chro­mosome lp(22) did occur in our case. Since reports of cytogenetic changes in pleomorphic RMS are scarce, no d istin c t association betw een cytogenetic abnormality and histo­logic type can be elucidated from this study.

Acknowledgment

We thank Mei L. Wu for her excellent secretarial assis­tance.

R eferences

1. Wick MR, Scheithauer BW, Smith SL, Beart RW Jr. Primary non-lymphoreticular malignant neoplasms of the spleen. Am J Surg Pathol 1982;6:229-242.

2. Gaffney EF, Dervan PA, Fletcher CDM. Pleomor­phic rhabdomyosarcoma in adulthood: analysis of 11

cases with definition of diagnostic criteria. Am J Surg Pathol 1993;17:601-609.

3. Hajdu SI. Pathology o f Soft Tissue Tumors. Philadel­phia, PA: Lea & Febiger; 1979.

4. Alpem HD, Olson JE, Kozak AJ. Inflammatory pseu­dotumor of the spleen. J Surg Oncol 1986;33:46-49.

5. Boram LH, Erlandson RA, Hajdu SI. Mesodermal mixed tumor of the uterus. Cancer 1972;30:1295-1306.

6 . Roncaroli F, Eusebi V. Rhabdomyoblastic differentia­tion in a leiomyosarcoma of the retroperitoneum. Hum Pathol 1996;27:310^U3.

7. Hagstrom L. Malignant mesenchymoma in pulmonary arteiy and right ventricle. Acta Pathol Microbiol Scand 1961;51:87-94.

8 . Hashimoto H, Daimaru Y, Tsuneyoshi M, Enjoji M. Soft tissue sarcoma with additional anaplastic compo­nents. Cancer 1990;66:1578-1589.

9. Suster S, Moran CA, Koss MN. Rhabdomyosarcomas of the anterior mediastinum: report of four cases unas­sociated with germ cell, teratomatous, or thymic car cinomatous components. Hum Pathol 1993;25:349-356.

10. Emmert-Buck MR, Stay EJ, Tsokos M, Travis WD. Pleomorphic rhabdomyosarcoma arising in association with the right pulmonary arteiy. Arch Pathol Lab Med 1994;118:1220-1222.

11. Hajdu SI, Lemos LB, Kozakewich H, Helson L, Beat­tie EJ Jr. Growth pattern and differentiation of human soft tissue sarcomas in nude mice. Cancer 1981;47: 90-98.

12. Wang-Wu S, Soukup S, Ballard E, Gotwals B, Lamp- kin B. Chromosomal analysis of sixteen human rhab­domyosarcomas. Cancer Res 1988;48:983-987.